FDA Update: June 2018

Jun 14, 2018

Express Scripts Office of Clinical Evaluation and Policy tracks some recent updates to the drug pipeline.

New Pill Bottle

Express Scripts’ Emerging Therapeutics team features several of the important actions taken by the U.S. Food and Drug Administration (FDA), last month:

New Indications for Tafinlar and Mekinist

The FDA has approved the Novartis drugs, Tafinlar® (dabrafenib) and Mekinist® (trametinib), to treat two different types of cancer that have mutations in the same gene, BRAF V600. Both are kinase inhibitors that affect different parts of the same pathway. Their first new indication, granted on April 30, 2018, is to treat melanoma that has tested positive for a BRAF V600 mutation, that has involved lymph nodes and that has been completely removed. The second new indication, as initial treatment for inoperable or metastatic anaplastic thyroid cancer (ATC), was approved on May 4. ATC is a rare, but aggressive, cancer with average expected survival of only five to 12 months at diagnosis. Both approvals were as Breakthrough Therapies and under Priority Reviews. For ATC, Tafinlar/Mekinist therapy has Orphan Drug status, as well. Recommended dosing for Mekinist is 2mg once a day; for Tafinlar, it is 150mg (two 75mg capsules) twice a day. They can be used separately, but together, they have previous indications for metastatic forms of BRAF V600-mutated melanoma and non-small cell lung cancer (NSCLC). Tafinlar is dispensed with a Medication Guide due to the possibility that taking it may cause other types of cancer, including cutaneous squamous cell carcinoma. Prescribing information for both drugs is available here.

Andexxa Approved to Reverse Anticoagulation

Portola Pharmaceuticals’ Andexxa® [coagulation factor Xa (recombinant), inactivated-zhzo] was approved by the FDA on May 3, 2018. It is the first drug indicated to reverse the anticoagulation effects of the direct factor Xa inhibitors, Eliquis® (apixaban – Bristol-Myers Squibb) and Xarelto® (rivaroxaban – Janssen), when patients have bleeding that cannot be controlled or that is life-threatening. It will be infused intravenously (IV) as a 400mg or 800mg dose targeted to 30mg/minute and then followed by 4mg/minute or 8mg/minute infusions for as long as two hours. In two clinical studies, Andexxa (also known as andexanet alfa) restored an average of at least 90 percent of normal coagulation for patients who received it. A boxed warning on its label cautions that it may cause blood clots, strokes, heart failure or death. Andexxa received Accelerated Approval, Orphan Drug status and a Breakthrough Therapy designation from the FDA. Launch will be in two phases, with a small initial release in early June and wider distribution planned for early in 2019 after the FDA approves manufacturing changes. Prescribing information is here.  

Epinephrine Autoinjector Shortages

On May 9, 2018, the FDA added Mylan Pharmaceuticals’ EpiPen® (epinephrine auto-injector, 0.3mg), EpiPen Jr® (epinephrine autoinjector, 0.15mg) and their authorized generics to its list of drugs in short supply. Citing manufacturing delays, Mylan stated that brief, unpredictable shortages may occur in random areas of the country, but that they are working with wholesalers and pharmacies to be sure enough autoinjectors are available to fill prescriptions as quickly as possible. However, patients who are experiencing difficulty filling prescriptions for EpiPen should contact Mylan Customer Relations at 800.796.9526 for assistance in locating alternative pharmacies.

In addition to EpiPen, both the 0.3mg and 0.15mg strengths of Adrenaclick® (epinephrine injector, auto-injector), made by Impax Laboratories, also are in shortage with no estimate of when supplies may be restocked. However, a third company, Kaleo, released information that all three strengths (0.3mg, 0.15 and 0.1mg) of Auvi-Q®, its epinephrine injection, are available. Patients who fill a prescription for an injector that is different from the one they usually use are advised to ask the pharmacist or doctor to show them how to activate the new device. More information on this shortage can be found by searching for “Epinephrine Injection, Auto-Injector” on FDA’s Drug Shortage website.

Approval Expanded for Gilenya

Novartis received Priority and Breakthrough approval from the FDA on May 11, 2018, for Gilenya® (fingolimod) to treat children as young as 10 years old. Gilenya is an oral, disease-modifying drug indicated for treating relapsing forms of multiple sclerosis (MS). It is a sphingosine 1-phosphate receptor modulator, which keeps white blood cells from reaching the central nervous system (CNS) where they could damage myelin, the protective covering around nerve fibers. Even though most cases of MS are diagnosed among adults from 20 to 40 years of age, the National MS Society estimates that between 8,000 and 10,000 American children have it. In general, MS progresses more slowly among children and teens. However, they may have more relapses than adults do. Recommended dosing for patients weighing at least 40Kg (88 pounds) is one 0.5mg capsule daily. Patients who weigh less should take 0.25mg per day. A Medication Guide given to patients outlines the side effects that may be associated with taking Gilenya. They include slow heart rate, higher risk of infections and vision problems. Full prescribing information is here.

FDA Approves Retacrit, a Biosimilar to Epogen/Procrit

On May 15, 2018, the FDA approved Hospira’s Retacrit (epoetin alfa-epbx), a biosimilar to Epogen® (Amgen) and Procrit® (Janssen). All three have the same indications -- for treating anemia caused by chronic kidney disease, chemotherapy, or the use of zidovudine in patients with HIV infection. They also are approved to reduce the chance that a red blood cell transfusion will be needed in patients undergoing elective, noncardiac, nonvascular surgery. The dose of Retacrit varies depending on the indication. While launch plans for Retacrit are unknown, Amgen’s patents on epoetin alfa are not expected to block its availability. Full prescribing information is available here.

Extended Indication for Truvada

The FDA approved Gilead’s Truvada® (emtricitabine/tenofovir disoproxil fumarate) on May 15, 2018, as pre-exposure prophylaxis (PrEP) for teens who are at risk for acquiring HIV-1 and who weigh at least 35 Kg (77 pounds). The company sought the expanded indication based on a study from the Centers for Disease Control and Prevention (CDC), which found that individuals between 13 and 24 years of age made up 21% of new HIV infection cases in 2016. A trial conducted for Gilead by the Adolescent Medicine Trials Network for HIV/AIDS included young men who were 15 to 17 years of age and who have sex with men. Once daily PrEP with Truvada demonstrated a similar safety profile for them as were seen in the adult Truvada trials. The labeling does carry boxed warnings that patients taking Truvada to prevent HIV-1 must be tested as negative for the virus before treatment starts and at least once every three months during therapy. Additionally, discontinuing it may rekindle the hepatitis B virus for patients who have or have had hepatitis B. A Medication Guide describing its use and potential side effects will be dispensed to every patient who receives a Truvada prescription. Updated prescribing information is here.

Lucemyra Approved to Alleviate Opioid Withdrawal Symptoms

Under a Priority Review and a Fast Track designation, US WorldMeds received FDA approval on May 16, 2018, for Lucemyra (lofexidine). Indicated to lessen the symptoms of opioid withdrawal for adults who stop taking opioids, it should be integrated into a comprehensive treatment plan that also includes behavioral components. A centrally-acting alpha-2 adrenergic agonist, it is the first non-opioid drug to be FDA approved for managing withdrawal. Recommended dosing is three tablets taken every five to six hours each day for about a week and then tapered down as symptom severity decreases. No more than 16 tablets should be taken in any 24-hour period and Lucemyra should not be used for longer than two weeks. US WorldMeds plans to launch Lucemyra in August. Complete prescribing information is here.

Generic Launched for Welchol Tablets

On May 16, 2018, Amneal Pharmaceuticals announced the launch of its AB-rated generic to Welchol® (colesevelam) 625mg tablets. Shortly after, Sun announced its launch of an authorized generic to compete in the market. The drug is a bile acid sequestrant approved to treat high blood cholesterol. The recommended dose is six tablets taken all at once or three tablets twice daily. Doses should be taken at the same time as a meal and with a full glass of water or other beverage. The powdered form of Welchol currently remains brand-only. According to IQVIA, sales for Welchol were approximately $526 million for the 12 months ending February 28, 2018. 

Aimovig Approved for Migraine Prevention

Amgen and Novartis’ Aimovig (erenumab-aooe) was approved by the FDA on May 17, 2018 for the prevention of migraine headaches for adults. Aimovig is the first FDA-approved drug that inhibits the activity of calcitonin gene-related peptide (CGRP), a protein-like substance that promotes vasodilation, inflammation and pain transmission. The recommended dose for Aimovig is 70mg, as a self-administered subcutaneous (SC) injection, once monthly. Some patients may benefit from monthly doses of 140mg administered as two consecutive SC injections of 70mg each. Amgen and Novartis planned to launch Aimovig within one week of its approval.

New Potassium-Lowering Agent Approved

The FDA approved AstraZeneca’s Lokelma (sodium zirconium cyclosilicate) for oral suspension on May 18, 2018, to treat adults who have hyperkalemia (blood potassium levels of 5 mEq/L or higher). Hyperkalemia is associated with chronic kidney disease, diabetes, heart failure and the use of certain heart medications. Lokelma sticks to potassium and, since it cannot be absorbed by the body, pulls potassium out with it. In a clinical trial, potassium levels returned to normal ranges within 48 hours for 92 percent of the patients treated with Lokelma (previously known as ZS-9). Recommended initial dosing is 10Gm three times a day until potassium levels normalize, but for no longer than two days. Doses then are reduced to 10Gm once a day for maintenance of optimal potassium levels. Doses can be adjusted if potassium falls too low or begins to rise. Lokelma will be dispensed in packets containing either 5Gm or 10Gm of granules that are mixed with water for administration. Launch and pricing plans have not yet been released. Complete prescribing information is here.

Doptelet Approved for Pre-Procedure Thrombocytopenia

On May 21, 2018, the FDA approved Doptelet® (avatrombopag) for the treatment of thrombocytopenia (platelet counts lower than 50,000mcg/L) in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure. Depending on a patient’s platelet count prior to a procedure, the recommended dose is 40mg (two tablets) or 60mg (three tablets) once daily with food for five consecutive days. Dosing should begin 10 to 13 days prior to the procedure and the procedure should be completed within five to eight days after the last dose. Dova Pharmaceuticals plans to launch Doptelet in June. Full prescribing information can be found here.  

Yonsa Approved for Prostate Cancer

Sun Pharma’s Yonsa® (abiraterone acetate) was approved by the FDA on May 22, 2018, to treat patients who have metastatic castration-resistant prostate cancer. It will be used along with methylprednisolone. Recommended dosing is 500mg, administered as four 125mg tablets, once daily in combination with methylprednisolone 4mg administered orally twice daily. Launch and pricing plans have not yet been announced. Complete prescribing information is available here.

Palynziq Approved for Phenylketonuria

BioMarin Pharmaceuticals received approval from the FDA on May 24, 2018, for Palynziq (pegvaliase-pqpz). It is indicated to lower blood levels of phenylalanine (Phe) for adult patients who have phenylketonuria (PKU). A rare, inherited metabolic disorder, PKU affects approximately 20,000 Americans, who lack the specific enzyme that processes Phe. Palynziq, the first drug to treat the cause of PKU, is a pegylated synthetic replacement for the missing enzyme. Pegylation modifies drugs to limit their breakdown by the body’s immune system. Recommended dosing is 2.5mg given subcutaneously (SC) once a week for four weeks, then raised gradually over five weeks or longer to a maintenance dose of 20mg once a day. Some patients may need to use 40mg/day, if Phe levels are not reduced adequately. Due to the chance that Palynziq may cause anaphylaxis (severe allergic responses), it has both a boxed warning and a risk evaluation and management strategy (REMS). It should be available by the end of June. Prescribing information is here.  

Cimzia Approved for Psoriasis

The FDA has approved an additional indication for UCB’s pegylated tumor necrosis factor (TNF) inhibitor, Cimzia® (certolizumab pegol). On May 24, 2018, its use was expanded to treat moderate-to-severe plaque psoriasis for adults who are eligible for phototherapy or systemic treatments. In three phase III clinical trials that involved more than one thousand patients, Cimzia showed effectiveness for patients who had not used a biological therapy before and also for those who had. Recommended dosing is two subcutaneous (SC) injections of 200 mg each, given at the same time, once every 14 days. Cimzia is already approved for several other inflammatory conditions, including ankylosing spondylitis (AS), Crohn's disease, psoriatic arthritis (PsA) and rheumatoid arthritis (RA). All drugs in the TNF inhibitor class carry a boxed warning that using them may raise the risk of serious infections, including tuberculosis. If used by children, the risk of lymphoma and other cancers may go up, as well. Prescribing information is here.

Imvexxy Approved to Relieve Symptoms of Menopause

On May 29, 2018, the FDA approved Imvexxy (estradiol vaginal inserts), which is made by TherapeuticsMD, Inc. The applicator-free inserts provide low doses (either 4mcg or 10mcg) of estradiol to treat moderate-to-severe dyspareunia (vaginal pain associated with sexual activity) that is caused by vaginal dryness and thinness after menopause. Recommended dosing is one insert daily for 14 days, then one insert twice a week thereafter. Launch will be in July at a price similar to the cost of vaginal estradiol products that currently are available on the U.S. market. Labeling for Imvexxy carries boxed warnings that are common to all estrogens, which includes an increased risk of breast or endometrial cancers, blood clots or strokes. When used along with a progestin, they may also contribute to cardiovascular (CV) conditions and possibly to dementia. Imvexxy’s complete prescribing information is here.  

Ulcerative Colitis Indication for Xeljanz

Pfizer’s Xeljanz® (tofacitinib) was FDA approved on May 30, 2018, to treat adult patients who have moderate-to-severe forms of ulcerative colitis (UC). The inflammatory condition is believed to affect about 900,000 Americans. Known as a Janus kinase (JAK) inhibitor, Xeljanz blocks JAK pathways that relay inflammatory signals within cells. Originally approved in November 2012, Xeljanz also has indications for psoriatic arthritis and rheumatoid arthritis. Its labeling includes a boxed warning about its potential risk of causing serious infections and cancers. Treatment with Xeljanz may also increase cholesterol levels, increase liver enzymes and decrease blood counts. To inform healthcare providers and patients about the serious risks associated with Xeljanz, it is dispensed under a risk evaluation and mitigation strategy (REMS) and with a Medication Guide. Updated prescribing information is here.

Combination Drug Approved to Treat Osteoarthritis Pain and High Blood Pressure

Kitov Pharmaceuticals received FDA approval on May 31, 2018, for Consensi, which combines 2.5mg, 5mg or 10mg of the calcium channel blocker, amlodipine, with 200mg of celecoxib, a cyclooxygenase-2 (COX-2) inhibiting non-steroidal anti-inflammatory drug (NSAID). It will be taken one time a day to treat both high blood pressure and pain caused by osteoarthritis. NSAIDs have a boxed warning that they may cause potentially serious cardiovascular and/or gastrointestinal (GI) side effects. Presently, no launch or pricing plans have been announced. Prescribing information is available here.  

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